← BioTransfer GEO Dataset Finder
GEO series

Characterization of the ocular inflammatory response to AAV reveals divergence by sex and age

GSE266332 Mus musculus (mouse) RNA-seq (gene expression) 64 samples Submitted 2025/01/29 Platform GPL19057
At a glance

RNA-seq (gene expression) · mouse · 64 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
64 samples: 18 conditions, mostly with about 4 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Characterization of the ocular inflammatory response to AAV reveals divergence by sex and ageMolecular therapy : the journal of the American Society of Gene Therapy · 2025
Summary (written by the submitters)
Recombinant adeno-associated virus (AAV) is the leading platform for gene therapy in ocular disease. Progress for gene therapy has been hindered by AAV-induced inflammation, which limits dose escalation and long-term efficacy. Characterisation of the ocular immune response to AAV in mice has been restricted to young animals and demonstrate activation of microglia, antigen presentation and a dominant T cell lymphocyte infiltration.
Read the full summary ↓
The extent of the inflammatory response alters with age and sex and these factors have not been fully represented in the pre-clinical development of ocular AAV gene therapies. Here, we intravitreally inject a null AAV2 vector in young (3-month), middle aged (9-month) and old (18-month) Cx3cr1-creER:R26tdTomato+/- mice of both sexes. Applying clinical imaging, flow cytometric analyses and bulk-sequencing of sorted resident microglia we interrogate the impact of sex and age on the longitudinal response of both microglia and infiltrating cellular response to AAV. Young animals have a dynamic response, with a peak in inflammation at D10-12 and signs of clinical resolution by D28. Despite similar kinetics in the inflammatory response between young male and females, sex differences are observed in the magnitude of the transcriptional response by microglia and the adaptive component of the infiltrating response. With age, the inflammation increases and persists after AAV2 injection. Based on the microglia transcriptional response to AAV, males maintain similar signature across age, although enhanced with increasing age. Contrary, females have greater divergence in their inflammatory response across age. Of particular note, old females have enriched cellular stress and inflammatory microglia gene signatures, with corresponding retinal degeneration. These findings inform crucial sex and age differences for therapeutic application of ocular gene therapy. Our dataset highlight the need to further define these differences to appropriately tackle AAV immunogenicity for all populations.
Published in
Characterization of the ocular inflammatory response to AAV reveals divergence by sex and age
Clare AJ, Langer PM, Ward A et al. · Molecular therapy : the journal of the American Society of Gene Therapy 2025 · PMID 39825566 · doi:10.1016/j.ymthe.2025.01.028
This dataset
Open GSE266332 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE266332_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1106775 and SRA study SRP505133. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39825566) ↗
Study design
18 conditions, mostly with about 4 replicates each
3m_Female_Naive ×4 3m_Male_D12 ×4 3m_Female_D12 ×4 9m_Male_D12 ×4 9m_Male_D28 ×4 18m_Female_D28 ×4 18m_Male_D28 ×4 18m_Female_D12 ×4 +10 more

Supports a between-group comparison across 64 samples.

How we read this: 18 replicated groups read from 64 sample titles; they account for 64 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 24 more — browse all 64 samples with per-sample file links →

Datasets on a similar topic

Search all mouse RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.